New Methods and Strategies for the Synthesis and Selective Derivatization of Natural Products

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Project Summary/Abstract These studies are focused on developing new catalytic approaches and strategies to improve the availability of cardiotonic steroids, bioactive terpenoids, and glycosylated natural product-based molecules of therapeutic value. Due to the importance of steroidal hormones for the regulation of vital biological processes in the human body, many members of the terpene family of natural products possess a wide spectrum of biological activities. In particular, cardiotonic steroids have many centuries-long history of serving as effective drugs for the treatment of various heart conditions. In addition, many recent studies suggest that these compounds hold great potential as the therapeutic agents for the treatment of cancer, inflammation, immune and metabolic diseases, and in various important health-related areas such as contraception. The developed in these studies new synthetic approaches could significantly improve the availability of otherwise difficult-to-access stereoisomeric cardenolide scaffolds with unusual substitution or oxidation patterns, and one of our objectives is to conduct the medicinal chemistry exploration of various natural and unnatural cardiotonic steroids. The techniques developed in this project will also improve the accessibility of related natural products such as bioactive plant- and bacteria- derived glycosylated steroids, and diterpenes of grayanotoxin, isopimarane and kuarane families. Finally, these studies will result in new catalytic techniques and strategies that will enable a direct and straightforward glycosylation of complex natural products. One of the important objectives of these studies will be developing new methods and catalysts for the asymmetric reactions that will enable the synthesis of natural products and therapeutic agents.